Teenagers, Drug Addiction, and Reward and Impulse Control

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- The risk for becoming addicted to drugs varies from person to person, even among those who use similar drugs in a similar way. Studies suggest that certain personality traits seen in people with drug addiction may be present before drug use. These traits include responding differently to rewards or impulsivity. Early use of drugs (before age 15) is also associated strongly with drug addiction later in life. Researchers want to study teenagers with and without certain behavioral problems, including those who have used drugs and those who have not. This may help them better understand behaviors that might predict future drug addiction.

Objectives:

- To understand brain function in teenagers who may be at a higher risk than others to drug addiction.

Eligibility:

Teenagers between 13 and 17 years of age who fit into one of four groups:

Have never or rarely used drugs

Have never or rarely used drugs and have conduct or behavior disorders

Have used drugs on many occasions

Have used drugs on many occasions and have conduct or behavior disorders

Design:

Participants will be screened with a medical history, and physical and neurological exams. They will also have blood and urine tests. Participants will answer questions about past drug use and any current medications. They will also have a breathalyzer and carbon monoxide breath test to check for recent drug and alcohol use.

This study requires four visits to the clinical center for magnetic resonance imaging (MRI) scans and other tests.

The first study visit will include training for the MRI scans. Participants will practice the tasks in front of a computer and in a mock (fake) MRI machine. Participants will also be asked several questions about their personality and past experiences.

Researchers will test changes to tryptophan and dopamine levels. Both of these chemicals affect decision making and brain function. On the three study visits, participants will have the following tests in a randomly selected order. One study will be done at each visit.

MRI scans with changes to dopamine and tryptophan levels

MRI scans with changes to dopamine only (with placebo)

MRI scans with changes to tryptophan only (with placebo)

Participants will be monitored with frequent blood draws and other tests during the study visits....

Condition or disease

AdolescentsConduct DisorderVulnerability to Substance Addicition

Detailed Description:

Background: Even under similar drug use patterns, the risk for drug addiction varies from individual to individual. However, the neurobiological mechanisms underlying this variability are poorly understood and characterized. Studies suggest that certain traits observed in substance dependent individuals may actually precede drug use, and could augur future substance dependence. Understanding how the presence of these traits increases vulnerability to substance addiction could aid in the development of early intervention, preventative measures, as well as better treatment strategies.

Objective: The primary goal of this protocol is to improve our understanding of increased susceptibility to developing substance addiction. We focus here on reward and punishment learning, and impulse control, with an emphasis on the underlying role of dopamine and serotonin function in these two cognitive functions. Further, given that cortical plasticity is enhanced during childhood and adolescence, we begin to address whether early exposure to substances enhances neurobiological changes that make an individual vulnerable to subsequent substance addiction.

Subject Population: We focus on adolescents (13-17 years old) with known increased vulnerability to substance addiction individuals with early exposure to substances, i.e. , those who have used drugs on multiple occasions before the age of 15, and those diagnosed with conduct disorder and who are not as yet substance dependent, along with matched controls.

Experimental Design: This study involves cognitive, pharmacological and functional magnetic resonance imaging (fMRI) testing in a mixed, within/between-subject design. Based upon power analyses, we estimate needing 30 participants in each of 4 groups early exposure (EE), conduct disorder (CD-NE), conduct disorder with early exposure (CD-EE), and controls with no early exposure (NE) to complete the experiment. This is a within subjects, placebo controlled, crossover design with participants tested before and after 1) cabergoline (D2 receptor agonist) treatment, 2) acute tryptophan depletion, and 3) placebo.

Outcome Measures: The primary outcome measures will be BOLD fMRI activation and behavioral performance on various cognitive tasks that deal with impulse control and reward learning before and after each of the three treatments listed above. Secondary outcome measures include gene x environment interactions and stress and novelty-seeking measures.

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Ages Eligible for Study:

13 Years to 17 Years (Child)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

INCLUSION CRITERIA:

All participants:

Between 13 and 17 years old (inclusive);

Must be able to provide informed assent and have a parent/guardian who can provide informed consent;